Tag Archives: tranexamic acid

TXA Hesitancy: Part II

In my last post, I reviewed a huge systematic review and meta-analysis of the use of tranexamic acid (TXA)  by all medical disciplines using it. There were more than 125,000 cases included and showed the incidence of thrombotic complications in TXA vs non-TXA patients was exactly the same at about 2%.

Our orthopedic surgery colleagues have been using TXA to reduce bleeding in their cases for decades. There is nothing close to the degree of “TXA hesitancy” in orthopedic surgeons than I see in surgical practices across trauma centers. What do the orthopods know that we don’t?

Trauma orthopedic groups in Malta and the UK published a paper just this month in which they performed a systematic review and meta-analysis of the use of TXA in hip fracture surgery. They focused on randomized, controlled trials published after 2010. A standard approach was used in the analysis, which looked specifically at the impact of IV TXA on transfusion requirements in surgery. Only adults were studied, and eligible studies compared TXA with a placebo, or TXA with no TXA.

Here are the factoids:

  • Out of 85 studies initially identified, only 13 met all criteria
  • Across these trials, a total of 1194 patients were enrolled
  • The need for blood transfusion was reduced by more than 50% when the transfusion threshold was Hgb 8g/dl, which was highly statistically significant
  • When a higher transfusion threshold was used (between 8-10 g/dl Hbg) the risk reduction was only 23% which was not significant
  • The incidence of thrombotic events was identical for TXA and no-TXA groups

Bottom line: This paper presents more high-quality evidence that the use of TXA in surgically induced injury (hip fracture repair) significantly reduces the need for transfusion in the group with the most blood loss. 

However, as with any meta-analysis the results are only as good as the quality of the individual papers. There were differences in how the TXA was given. It was also not possible to separate out results from the various types of hip surgery performed. And obviously, these are not major, multi-trauma patients.

Most TXA hesitant surgeons are either concerned with the efficacy of TXA, or the potential risks. This paper shows that, overall, TXA is effect in these patients despite the mix of doses and timing of delivery. And it clearly shows that the risk for thrombotic complications was identical to that of not giving it.

We have a cheap, effective tool to reduce the need for blood transfusion (read “blood loss”) in trauma patients that has a totally neutral risk profile for thrombosis. We all need to ask ourselves, “why are we not using it?”

Reference: The Use of Tranexamic Acid in Hip Fracture Surgery — A
Systematic Review and Meta-analysis . J Orthop Trauma, 36(2):e442-3448, 2022.

TXA Hesitancy: Part I

I’ve visited several hundred trauma centers over the past 25 years, and recently I’ve begun to appreciate that there are two tribes when it comes to the use of tranexamic acid: the TXA believers and the TXA hesitant.

There have been a number of large studies that seem to suggest a benefit with respect to survival from major hemorrhage, particularly if given soon after injury (CRASH-2, MATTERs). This drug is dirt cheap and has been around a long time, so it has a clearly defined risk profile.

However, many of those hesitant to use it point to the possibility of thromboembolic events that have been sporadically reported. Several years ago, I did my own literature review and found that the number of thrombotic events from TXA was nearly identical to that of transfusing plasma.

JAMA Surgery published a large systematic review, meta-analysis, and meta-regression last year that sought to examine the association between thromboembolic events (TE) in patients of any age and involving all medical disciplines, not just trauma.

The anesthesia group at the University Hospital Frankfurt in German did a systematic search of the Cochrane Central Register of Controlled Trials, as well as MEDLINE, for randomized controlled trials involving TXA. They covered all published studies through December 2020.

The authors adhered to standard guidelines for conducting reviews and meta-analysis (PRISMA). They specifically searched for outcomes involving TEs, such as venous thromboembolism, myocardial infarction or ischemia, limb ischemia, mesenteric thrombosis, and hepatic artery thrombosis. They also tallied the overall mortality, bleeding mortality, and non-bleeding mortality.

Here are the factoids:

  • A total of 216 eligible trials were identified that included over 125,000 patients (!)
  • Total TEs in the TXA group were 1,020 (2.1%) vs 900 (2.0%) in the control group
  • Studies at lowest risk for selection bias showed similar results

Bottom line: The authors concluded that IV TXA, irrespective of the dose, does not increase the risk of thromboembolic events. Period.

In my next post I’ll describe an even more recent systematic review and meta-analysis in orthopedic patients. Our orthopedic colleagues have been using this drug successfully for hip surgery for decades. Let’s see what they think.

Reference: Association of Intravenous Tranexamic Acid With Thromboembolic Events and Mortality A Systematic Review, Meta-analysis, and Meta-regression. JAMA Surgery 156(6):3210884, 2021.

TXA, Thromboembolic Events, And Mortality

I’ve visited several hundred trauma centers over the past 25 years, and recently I’ve begun to appreciate that there are two camps  when it comes to the use of tranexamic acid: the TXA believers and the TXA hesitant.

There have been a number of large studies that seem to suggest a benefit with respect to survival from major hemorrhage, particularly if given soon after injury (CRASH-2, MATTERs). This drug is dirt cheap and has been around a long time, so it has a clearly defined risk profile.

However, many of those hesitant to use it point to the possibility of thromboembolic events that have been sporadically reported. Several years ago, I did my own literature review and found that the number of thrombotic events from TXA was nearly identical to that of transfusing plasma.

JAMA Surgery just published a large systematic review, meta-analysis, and meta-regression that sought to examine the association between thromboembolic events (TE) in patients of any age and involving all medical disciplines, not just trauma.

The anesthesia group at the University Hospital Frankfurt in German did a systematic search of the Cochrane Central Register of Controlled Trials, as well as MEDLINE, for randomized controlled trials involving TXA. They covered all published studies through December 2020.

The authors adhered to standard guidelines for conducting reviews and meta-analysis (PRISMA). They specifically searched for outcomes involving TEs, such as venous thromboembolism, myocardial infarction or ischemia, limb ischemia, mesenteric thrombosis, and hepatic artery thrombosis. They also tallied the overall mortality, bleeding mortality, and non-bleeding mortality.

Here are the factoids:

  • A total of 216 eligible trials were identified that included over 125,000 patients (!)
  • Total TEs in the TXA group were 1,020 (2.1%) vs 900 (2.0%) in the control group
  • Studies at lowest risk for selection bias showed similar results

Bottom line: The authors concluded that IV TXA, irrespective of the dose, does not increase the risk of thromboembolic events. Period.

Hopefully, this is the final study needed to convince the TXA hesitant that it is safe to administer. They may still argue the efficacy, but at less than $100 per vial it is becoming impossible to ignore.

Reference: Association of Intravenous Tranexamic Acid With Thromboembolic Events and Mortality A Systematic Review, Meta-analysis, and Meta-regression. JAMA Surgery 156(6):3210884, 2021.

Papers To Change Our Practice 1: Tranexamic Acid

The first paper I’ll be presenting on Friday at the Penn Reunion deals with tranexamic acid (TXA). This drug works differently than the quick clotting agents out there. It’s an antifibrinolytic, so it actually prevents clot breakdown. It has been approved by the FDA for use in hemophiliacs undergoing dental work and for menorrhagia. Thrombotic complications have been described, so it cannot be used with prothrombin complex concentrate or recombinant activated factor VII.

The most recent and best known study on TXA is the CRASH-2 study. It was extremely well designed and included over 20,000 patients in hospitals spanning 40 countries. The study design has survived serious scrutiny. They found that TXA use in trauma patients reduced the relative risk of death by 9% (from 16% to 14.5%). The risk of death specifically from bleeding was reduced by 15%. And use of TXA in the most severely injured patients, those who would die of bleeding on the day of randomization, was reduced by 20%. CRASH-2 suggested that TXA was of most benefit when given within 3 hours of injury and in patients with a systolic pressure less than or equal to 75 torr. There were no adverse events or differences in thrombotic events, including deep venous thrombosis.

Bottom line: TXA has been shown to be effective, safe and inexpensive (about $200 for treatment using retail pricing). It is the only drug that has been shown to reduce all-cause mortality from bleeding in a high quality trial. And it only needs to be used in 67 major trauma patients before one life will be saved. It has already been adopted by some hospitals in both the US and the UK. Trauma centers should begin to think about incorporating this important drug into their initial treatment protocols now. HOWEVER: Since it is not FDA approved in the US, we may have to wait a little longer here to start using it in earnest. And think about the possibilities when EMS can start giving it in the field!

Reference: Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial. Lancet. 2010;376:23–32.